4-苯基丁酸对果糖所致非酒精性脂肪肝的保护效应

The protective effect of 4-phenyl butyrate acid on fructose-evoked nonalcoholic fatty liver disease in mice

目的探讨4-苯基丁酸(PBA)对饮用果糖所致小鼠非酒精性脂肪肝的保护作用。方法 48只♀ICR小鼠随机分为4组。对照组给予普通自来水喂养8周;果糖组给予30%果糖水溶液喂养8周;PBA组给予普通自来水喂养8周,最后2周经腹腔注射给予PBA(100 mg.kg-1);PBA+果糖组给予富含30%果糖水溶液喂养8周,最后2周经腹腔注射给予PBA(100 mg.kg-1)。各组小鼠均自由进食标准饲料。实验结束后立即剖杀小鼠,采集血清和肝组织,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TCH)、甘油三酯(TG)、高密度脂蛋白(HDL)、极低密度脂蛋白(VLDL)和肝脏组织TCH和TG;HE染色分析肝脏组织病理学改变;油红O染色分析肝脏脂质沉积。RT-PCR测定小鼠肝脏脂肪酸合成酶(fas)、乙酰辅酶A羧化酶(acc)和硬脂酰辅酶A去饱和酶-1(scd-1)mRNA表达。结果与对照组相比,果糖组小鼠血清和肝脏TG及肝脏TCH的含量明显升高;HE染色显示,果糖组小鼠肝细胞脂肪变性;油红O染色证实,果糖组小鼠肝脏有明显脂质沉积;进一步研究显示,与对照组相比,果糖组小鼠肝脏fas,acc和scd-1 mRNA水平均明显上调。果糖组与PBA+果糖组比较显示,PBA干预可明显降低血清、肝脏TG含量及肝脏TCH含量,减轻果糖引起的肝脏脂质沉积;抑制果糖引起的肝脏fas,acc和scd-1表达上调。结论 PBA对饮用果糖所致的小鼠非酒精性脂肪肝有保护作用。

Aim To investigate the protective effect of 4-phenyl butyric acid（PBA） on fructose-induced nonalcoholic fatty liver disease in mice.Methods 48 female ICR mice were randomly divided into 4 groups.In control group,mice had free access to tap water for eight weeks;In fructose group,mice had free access to tap water containing 30% fructose for eight weeks;in PBA group,mice had free access to tap water for eight weeks and were intraperitoneally injected with PBA（100 mg·kg^-1） in the last two weeks;in PBA＋fructose group,mice had free access to tap water containing 30% fructose for eight weeks and intraperitoneally injected with PBA（100 mg·kg^-1） in the last two weeks.All mice were fed regular diet.Mice were killed to collect serum and liver specimens.Serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,total cholesterol（TCH）,triglycerides（TG）,high density lipoprotein（HDL）,very low density lipoprotein（VLDL） and hepatic TCH and TG were determined.HE staining and oil red O staining were carried out to assess the change of hepatic histology and lipid accumulation.RT-PCR was used to detect the level of hepatic fatty acid synthase（fas）,acetyl coenzyme A carboxylase（acc） and stearoyl coenzyme A desaturase-1（scd-1） mRNA.Results The level of serum and hepatic TG and hepatic TCH was significantly increased in fructose-fed mice.An obvious hepatic lipid accumulation was observed.PBA significantly alleviated fructose-induced elevation of serum and hepatic TG content and hepatic TCH content.In addition,PBA attenuated fructose-induced hepatic lipid accumulation.Moreover,PBA inhibted fructose-induced upregulation of hepatic acc,fas and scd-1.Conclusion PBA protects mice from fructose-induced nonalcoholic fatty liver disease.